Effects of Enalapril and Clonidine on Glomerular Structure, Function, and Atrial Natriuretic Peptide Receptors in SHHF/Mcc-cp Rats

Mj, Radin; Je, Jenkins; Sa, McCune; Rr, Jurin; Rl, Hamlin

doi:10.1097/00005344-199203000-00026

Cited by 15 publications

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“…For comparison, similar samples were obtained from age-matched male WF rats. ANP was measured by using a modification of a commercially available radioimmunoassay kit (Peninsula Laboratories, Belmont, CA) (27).…”

Section: Methodsmentioning

confidence: 99%

“…Still, the role of sex hormones in the development and control of hypertension and subsequent heart failure remains controversial. Sexual dimorphism in the pattern of neurohumoral activation may have consequences on the rate of cardiac remodeling and decompensation, as well as on response to therapy (6,26,27,30) and survival (1).The spontaneous hypertensive heart failure rat (SHHF/Mcc-fa cp or SHHF) is a multifactoral, genetic model of hypertension and CHF. Despite a similar genetic predisposition to the development of hypertension and heart failure, male SHHF rats develop and die from overt CHF at an earlier age compared with female rats (12,19,20).…”

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“…Significant decline in cardiac function occurs in female SHHF rats after they cease to cycle, and serum estrogen concentrations begin to fall (31). Furthermore, female SHHF rats respond differently to various classes of antihypertensive drugs compared with male rats, suggesting mechanistic differences in control of hypertension (6,26,27,30).We examined the influence of gender on plasma renin activity (PRA), serum angiotensin-converting enzyme (ACE) activity, urinary endothelin excretion, and plasma ANP concentrations in lean male and female SHHF rats at a time when hypertension was established but before cardiac decompensation. Additionally, these same parameters were investigated during the period of cardiac decompensation and onset of CHF.…”

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Gender modulates activation of renin-angiotensin and endothelin systems in hypertension and heart failure

Radin¹,

Holycross²,

Sharkey

et al. 2002

Journal of Applied Physiology

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. Gender modulates activation of renin-angiotensin and endothelin systems in hypertension and heart failure. J Appl Physiol 92: 935-940, 2002. First published October 19, 2001 10.1152/ japplphysiol.00558.2001.-Sexual dimorphism may occur during the development of hypertension and congestive heart failure (CHF). Male and female spontaneous hypertension heart failure (SHHF) rats with established hypertension, but before CHF (age 5-8 mo) and during cardiac decompensation leading to CHF (age 18-20 mo in male rats and 22-24 mo in female rats), were studied. At 5-8 mo, male SHHF rats showed early activation of the renin-angiotensin system (RAS), as indicated by increased plasma renin activity (PRA) and higher serum angiotensin-converting enzyme activity compared with female rats. The increase in PRA in female rats was delayed compared with males rats, but it reached comparable levels just before CHF. Urinary endothelin excretion was significantly greater in 5-to 8-mo-old female rats compared with age-matched male rats. Urinary endothelin excretion increased in both male and female rats as CHF developed. Plasma atrial natriuretic peptide (ANP) was comparable at both time points, and both genders showed similar, marked increases as CHF developed. In conclusion, male rats show early activation of the RAS, whereas female rats show early activation of the endothelin vasopressor system. During cardiac decompensation, generalized activation of the RAS, endothelin, and ANP systems occurs and is similar in male and female SHHF rats. plasma renin activity; atrial natriuretic peptide; spontaneous hypertension heart failure HYPERTENSION IS AN IMPORTANT risk factor for the development of congestive heart failure (CHF). Development of hypertension and CHF is associated with activation of multiple neuroendocrine systems, including the renin-angiotensin (RAS), endothelin, and atrial natriuretic peptide (ANP) systems (3,9,18,33). However, various demographic factors such as age, race, and gender have been implicated in modulating the pattern of vasoconstrictor and vasodilator activation observed in an individual and may influence the importance of a neurohumoral system in the pathophysiology of cardiac hypertrophy and decompensation (35). Many studies have implicated sex hormones as modulators of risk factors for cardiovascular disease (7). In humans, men tend to develop hypertension and subsequent heart failure at an earlier age compared with women (1, 16). Onset of cardiovascular disease in women is frequently delayed until after menopause (7,23). Still, the role of sex hormones in the development and control of hypertension and subsequent heart failure remains controversial. Sexual dimorphism in the pattern of neurohumoral activation may have consequences on the rate of cardiac remodeling and decompensation, as well as on response to therapy (6,26,27,30) and survival (1).The spontaneous hypertensive heart failure rat (SHHF/Mcc-fa cp or SHHF) is a multifactoral, genetic model of hypertension and CHF. Despite a similar genetic predi...

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Gender modulates activation of renin-angiotensin and endothelin systems in hypertension and heart failure

Radin¹,

Holycross²,

Sharkey

et al. 2002

Journal of Applied Physiology

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Treatment of Obese Female and Male SHHF/Mcc‐fa^cp Rats with Antihypertensive Drugs, Nifedipine and Enalapril: Effects on Body Weight, Fat Distribution, Insulin Resistance and Systolic Pressure

et al. 1993

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Little is known about the effects of common antihypertensive drugs in obese, insulin-resistant females. Nine-month-old obese female SHHF/Mcc-fa(cp) rats that received either nifedipine, a calcium channel antagonist, or enalapril, an angiotensin-converting-enzyme inhibitor, for three months were compared with untreated SHHF/Mcc-fa(cp) rats (controls). After one month, nifedipine significantly decreased body weight in obese females compared to either enalapril or controls. After three months of treatment, total, abdominal, and subcutaneous fat masses were decreased in obese females given nifedipine compared to either enalapril or controls. Enalapril treatment was associated with a redistribution of fat mass from abdominal to subcutaneous depots. Nifedipine reduced plasma triglyceride and fasting glucose levels and improved insulin response to an oral glucose load in obese females, whereas enalapril did not appear to affect glycemic control. Systolic pressure was not significantly decreased until after two months of treatment with nifedipine or three months of treatment with enalapril in obese females and may have coincided with improvement in insulin-resistance. Similarly, plasma atrial natriuretic peptide concentrations were significantly lower in obese females given nifedipine. To determine how obese males responded to a calcium channel antagonist, six-month-old obese male SHHF/Mcc-fa(cp) rats were treated for three months with either nifedipine or placebo (controls). Nifedipine-treated obese males showed a mild but significant decrease in weight gain that was due to a decrease in fat deposition in both subcutaneous and abdominal depots and systolic blood pressure was significantly reduced after one month of treatment. Nifedipine did not affect other plasma biochemical parameters in obese males. In conclusion, nifedipine improved systolic pressure and glycemic control in obese female SHHF/Mcc-fa(cp) rats, effects that may be associated with a marked loss in body weight and fat mass and improved lipid metabolism. Nifedipine-treated obese males exhibited only a diminished weight gain that was not associated with changes in diabetic characteristics.

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Effect of Ovariectomy and Estrogen Replacement on Cardiovascular Disease in Heart Failure-Prone SHHF/Mcc- fa cp Rats

Sharkey

Holycross

Park

et al. 1999

Journal of Molecular and Cellular Cardiology

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Effects of Enalapril and Clonidine on Glomerular Structure, Function, and Atrial Natriuretic Peptide Receptors in SHHF/Mcc-cp Rats

Cited by 15 publications

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Gender modulates activation of renin-angiotensin and endothelin systems in hypertension and heart failure

Gender modulates activation of renin-angiotensin and endothelin systems in hypertension and heart failure

Treatment of Obese Female and Male SHHF/Mcc‐fa^cp Rats with Antihypertensive Drugs, Nifedipine and Enalapril: Effects on Body Weight, Fat Distribution, Insulin Resistance and Systolic Pressure

Effect of Ovariectomy and Estrogen Replacement on Cardiovascular Disease in Heart Failure-Prone SHHF/Mcc- fa cp Rats

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Effects of Enalapril and Clonidine on Glomerular Structure, Function, and Atrial Natriuretic Peptide Receptors in SHHF/Mcc-cp Rats

Cited by 15 publications

References 0 publications

Gender modulates activation of renin-angiotensin and endothelin systems in hypertension and heart failure

Gender modulates activation of renin-angiotensin and endothelin systems in hypertension and heart failure

Treatment of Obese Female and Male SHHF/Mcc‐facp Rats with Antihypertensive Drugs, Nifedipine and Enalapril: Effects on Body Weight, Fat Distribution, Insulin Resistance and Systolic Pressure

Effect of Ovariectomy and Estrogen Replacement on Cardiovascular Disease in Heart Failure-Prone SHHF/Mcc- fa cp Rats

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Treatment of Obese Female and Male SHHF/Mcc‐fa^cp Rats with Antihypertensive Drugs, Nifedipine and Enalapril: Effects on Body Weight, Fat Distribution, Insulin Resistance and Systolic Pressure